Drug-related stimuli can elicit drug craving in drug abusers and have been implicated in relapse. An important objective of drug abuse treatment is to reduce or eliminate the control that these cues have over individuals. The goal of the research proposed here is to use an animal model to develop procedures that can be used to effectively treat drug cues. Specifically, we will investigate techniques for temporarily restoring or amplifying the expectation-outcome error signal produced by non-reinforcement as a means of enhancing extinction and conditioned inhibition of drug seeking. The first aim of the proposed research is to develop a way to deepen the extinction of drug cues by using combinations of drug- as well as non-drug- related stimuli to increase the error signal generated during extinction learning. A second aim is to create similar procedures that deepen the conditioned inhibition of drug seeking. A third aim is to deepen the extinction of drug cues by pharmacologically-reinstating the effects of a previously extinguished drug cue prior to exposing that cue to additional, extensive extinction. Achieving these aims could (1) provide insight into ways of enhancing the extinction and conditioned inhibition of drug seeking via behavioral and pharmacological interventions, and (2) form the empirical basis for the creation of an effective extinction- based treatment for drug abuse, a major public health problem. PUBLIC HEALTH RELEVANCE: The proposed research will investigate methods for reducing and ultimately eliminating the power that drug-associated stimuli have over drug users. Such stimuli have been shown to produce drug craving and have been implicated in relapse. Therefore, this research could lead to the development of effective treatments for drug abuse, a major public health problem.